Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia

VA Office of Research and Development

Status and phase: Completed; Phase 2; Phase 1

Conditions: Schizophrenia

Treatments: Drug: Placebo; Drug: Levetiracetam

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT03034356

I01CX001414 (U.S. NIH Grant/Contract)

MHBB-006-16S

Details and patient eligibility

About

This study plans to learn more about the effects of levetiracetam (LEV) on brain activity and cognition in schizophrenia and schizoaffective disorder. Levetiracetam is an anti-seizure drug, also called an anticonvulsant.

Full description

Cognitive symptoms are not currently well-managed in Veterans with schizophrenia, leading to substantially diminished quality of life. Improved treatment strategies clearly are needed. Recent studies suggest taht an overactive hippocampus is associated with cognitive deficits in the illness. Based on findings that the anti-epileptic drug levetiracetam (LEV) reduces hippocampal activity and improves cognition in other clinical populations while being safe and well-tolerated, this study will examine the effects of the drug on hippocampal activity and cognition in Veterans with schizophrenia. In this crossover design, participants will take LEV for 4 weeks and placebo pills for 4 weeks, but will not know the order in which they are taking them.

Enrollment: 67 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Diagnosis of schizophrenia or schizoaffective disorder
• Good general health
• Normal vital signs (blood pressure, pulse, respiration)

Exclusion criteria

• Substance abuse

• Significant neurological disorders

• Significant head trauma/injury

• Pregnancy

• MRI-specific exclusion criteria, e.g.,:

  • claustrophobia
  • weight>400 lbs
  • metal in the body

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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67 participants in 2 patient groups

Levetiracetam, Then Placebo

Experimental group

Description:

4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid).

Treatment:

Drug: Placebo

Drug: Levetiracetam

Placebo, Then Levetiracetam

Experimental group

Description:

4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid).

Treatment:

Drug: Placebo

Drug: Levetiracetam